PLoS Genetics最新文献

{"title":"PBX1 and PBX3 transcription factors regulate SHH expression in the Frontonasal Ectodermal Zone through complementary mechanisms.","authors":"Chan Hee Mok, Diane Hu, Marta Losa, Maurizio Risolino, Licia Selleri, Ralph S Marcucio","doi":"10.1371/journal.pgen.1011315","DOIUrl":"10.1371/journal.pgen.1011315","url":null,"abstract":"<p><p>Sonic hedgehog (SHH) signaling from the Frontonasal Ectodermal Zone (FEZ) is a key regulator of craniofacial morphogenesis. Along with SHH, pre-B-cell leukemia homeobox (PBX) transcription factors regulate midfacial development. PBXs act in the epithelium during fusion of facial primordia, but their specific interactions with SHH have not been investigated. We hypothesized that PBX1/3 regulate SHH expression in the FEZ by activating or repressing transcription. The hypothesis was tested by manipulating PBX1/3 expression in chick embryos and profiling epigenomic landscapes at early developmental stages. PBX1/3 expression was perturbed in the chick face beginning at stage 10 (HH10) using RCAS viruses, and the resulting SHH expression was assessed at HH22. Overexpressing PBX1 expanded the SHH domain, while overexpressing PBX3 resulted in an opposite effect. Conversely, reducing PBX1 expression decreased SHH expression, but reducing PBX3 induced ectopic SHH expression. We performed ATAC-seq and mapped binding of PBX1 and PBX3 to DNA with ChIP-seq on the FEZ at HH22 to assess direct interactions of PBX1/3 with the SHH locus. These multi-omics approaches uncovered a 400 bp PBX1-enriched element within intron 1 of SHH (chr2:8,173,222-621). Enhancer activity of this element was demonstrated by electroporation of reporter constructs in ovo and luciferase reporter assays in vitro. When bound by PBX1, this element upregulates transcription, while it downregulates transcription when bound by PBX3. The present study identifies a cis-regulatory element, named SFE1, that interacts with PBX1/3 either directly or within a complex with cofactors to modulate SHH expression in the FEZ. This research establishes that PBX1 and PBX3 play complementary roles in SHH regulation during embryonic development.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011315"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: A functional regulatory variant of MYH3 influences muscle fiber-type composition and intramuscular fat content in pigs.","authors":"In-Cheol Cho, Hee-Bok Park, Jin Seop Ahn, Sang-Hyun Han, Jae-Bong Lee, Hyun-Tae Lim, Chae-Kyoung Yoo, Eun-Ji Jung, Dong-Hwan Kim, Wu-Sheng Sun, Yuliaxis Ramayo-Caldas, Sang-Geum Kim, Yong-Jun Kang, Yoo-Kyung Kim, Hyun-Sook Shin, Pil-Nam Seong, In-Sul Hwang, Beom-Young Park, Seongsoo Hwang, Sung-Soo Lee, Youn-Chul Ryu, Jun-Heon Lee, Moon-Suck Ko, Kichoon Lee, Göran Andersson, Miguel Pérez-Enciso, Jeong-Woong Lee","doi":"10.1371/journal.pgen.1011715","DOIUrl":"10.1371/journal.pgen.1011715","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pgen.1008279.].</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011715"},"PeriodicalIF":4.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA duplication in Burkholderia thailandensis induces biofilm formation by activating a two-component regulatory system.","authors":"Lillian C Lowrey, Katlyn B Mote, Peggy A Cotter","doi":"10.1371/journal.pgen.1011528","DOIUrl":"10.1371/journal.pgen.1011528","url":null,"abstract":"<p><p>Burkholderia thailandensis strain E264 (BtE264) and close relatives stochastically duplicate a 208.6 kb region of chromosome I via RecA-dependent recombination between two nearly identical insertion sequence elements. Because homologous recombination occurs at a constant, low level, populations of BtE264 are always heterogeneous, but cells containing two or more copies of the region (Dup+) have an advantage, and hence predominate, during biofilm growth, while those with a single copy (Dup-) are favored during planktonic growth. Moreover, only Dup+ bacteria form 'efficient' biofilms within 24 hours in liquid medium. We determined that duplicate copies of a subregion containing genes encoding an archaic chaperone-usher pathway pilus (csuFABCDE) and a two-component regulatory system (bfmSR) are necessary and sufficient for generating efficient biofilms and for conferring a selective advantage during biofilm growth. BfmSR functionality is required, as deletion of either bfmS or bfmR, or a mutation predicted to abrogate phosphorylation of BfmR, abrogates biofilm formation. However, duplicate copies of the csuFABCDE genes are not required. Instead, we found that BfmSR controls expression of csuFABCDE and bfmSR by activating a promoter upstream of csuF during biofilm growth or when the 208.6 kb region, or just bfmSR, are duplicated. Single cell analyses showed that duplication of the 208.6 kb region is sufficient to activate BfmSR in 75% of bacteria during planktonic (BfmSR 'OFF') growth conditions. Together, our data indicate that the combination of deterministic two-component signal transduction and stochastic, duplication-mediated activation of that TCS form a bet-hedging strategy that allows BtE264 to survive when conditions shift rapidly from those favoring planktonic growth to those requiring biofilm formation, such as may be encountered in the soils of Southeast Asia and Northern Australia. Our data highlight the positive impact that transposable elements can have on the evolution of bacterial populations.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011528"},"PeriodicalIF":4.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incomplete paralog compensation generates selective dependency on TRA2A in cancer.","authors":"Amanda R Lee, Anna Tangiyan, Isha Singh, Peter S Choi","doi":"10.1371/journal.pgen.1011685","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011685","url":null,"abstract":"<p><p>Paralogs often exhibit functional redundancy, allowing them to effectively compensate for each other's loss. However, this buffering mechanism is frequently disrupted in cancer, exposing unique paralog-specific vulnerabilities. Here, we identify a selective dependency on the splicing factor TRA2A. We find that TRA2A and its paralog TRA2B are synthetic lethal partners that function as widespread and largely redundant activators of both alternative and constitutive splicing. While loss of TRA2A alone is typically neutral due to compensation by TRA2B, we discover that a subset of cancer cell lines are highly TRA2A-dependent. Upon TRA2A depletion, these cell lines exhibit a lack of paralog buffering specifically on shared splicing targets, leading to defects in mitosis and cell death. Notably, TRA2B overexpression rescues both the aberrant splicing and lethality associated with TRA2A loss, indicating that paralog compensation is dosage-sensitive. Together, these findings reveal a complex dosage-dependent relationship between paralogous splicing factors, and highlight how dysfunctional paralog buffering can create a selective dependency in cancer.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011685"},"PeriodicalIF":4.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An antisense RNA regulates production of DnaA and affects sporulation in Bacillus subtilis.","authors":"Emma L Sedivy, Janet L Smith, Alan D Grossman","doi":"10.1371/journal.pgen.1011625","DOIUrl":"10.1371/journal.pgen.1011625","url":null,"abstract":"<p><p>DnaA is the replication initiator and a transcription factor in virtually all bacteria. Although the synthesis and activity of DnaA are highly regulated, the mechanisms of regulation vary between organisms. We found that production of DnaA in Bacillus subtilis is regulated by an antisense RNA that overlaps with the 5' untranslated region upstream of the dnaA open reading frame. We initially observed this RNA in in vitro transcription experiments and found that its production was inhibited by DnaA. This RNA, now called ArrA for antisense RNA repressor of dnaA, is made in vivo. We identified the arrA promoter and made a mutation that greatly reduced (or eliminated) production of ArrA RNA in vitro and in vivo. In vivo, this arrA promoter mutation caused an increase in the amount of mRNA and protein from dnaA and dnaN, indicating that arrA expression normally inhibits expression of the dnaA-dnaN operon. The arrA mutation also caused a delay in sporulation that was alleviated by loss of sda, a sporulation-inhibitory gene that is directly activated by DnaA. arrA appears to be conserved in some members of the Bacillus genus, indicating that arrA has evolved in at least some endospore-forming bacteria to modulate production of DnaA and enable timely and robust sporulation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011625"},"PeriodicalIF":4.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights into region-specific sexual dichromatism: Comparative transcriptome analysis of red cheek pigmentation in zebra finches.","authors":"Gee-Way Lin, Chih-Kuan Chen, Ting-Xin Jiang, Ya-Chen Liang, Pin-Chi Tang, Ping Wu, Randall B Widelitz, Chih-Feng Chen, Cheng-Ming Chuong","doi":"10.1371/journal.pgen.1011693","DOIUrl":"10.1371/journal.pgen.1011693","url":null,"abstract":"<p><p>Feathers, the primary skin appendage covering the avian body, undergo dynamic phenotypic changes throughout a bird's life. Males and females of the same species can exhibit sexually dichromatic plumage colors which play a critical role in mating choice, survival, and ecological interactions. In this study, we investigate the molecular mechanisms underlying the changes of color that occur during the transition from juvenile to adult feathers, known as the secondary transition. We focus on sexual dichromatism of craniofacial plumage and use the male cheek domain of the zebra finch (Taeniopygia guttata) as the major model. The transcriptome of the cheek and scalp (crown) domains in males and females of wild-type and genetic color variants were compared. We found that (1) Craniofacial color patterning operates through two regulatory layers. The first layer involves transcription factor (TF) genes that define the cheek domain such as PITX1, PAX1, PAX6. The second layer comprises pigment-related genes responsible for specific colors, including male-biased TFs (SOX10 and DMRT1) and transporters associated with red pigment synthesis. (2) Surprisingly, ASIP, which controls pheomelanin production in other species, was expressed in both male (red) and female (gray) cheeks. Instead, PAX1 in cheek dermal fibroblasts may serve as an upstream regulator, potentially triggering the male-biased color pattern through PAX6 and SOX10. PAX6 and SOX10 in melanocytes potentially enhance the expression of GPR143, SLC45A2, and TMEM163, driving increased pheomelanin production in males. (3) Sexual dichromatism is associated with sex-linked genes on the Z chromosome, notably SLC45A2. In addition, motif analysis comparing the binding strength between regional transcription factors and melanogenesis genes suggests that craniofacial pigmentation may have evolved convergently in passerine birds. These findings provide novel insights into the molecular control of color patterning and lay the groundwork for further studies on avian sexual dichromatism and secondary feather transition.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011693"},"PeriodicalIF":4.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Heterozygosity associated with ubiquitous environments in yeast.","authors":"Nikilesh Vijayan, Sameer Joshi, Praseetha Sarath, Koodali T Nishant","doi":"10.1371/journal.pgen.1011692","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011692","url":null,"abstract":"<p><p>The effect of ubiquitous environmental conditions on mutational mechanisms, particularly loss of heterozygosity (LOH) remains poorly understood. Environment induced LOH can rapidly alter the genome and promote disease progression. Using mutation accumulation (MA) lines, we analysed the effect of ubiquitous environmental conditions on mutational mechanisms in a diploid hybrid (S288c/YJM789) baker's yeast strain. These included blue light, low glucose (calorie restriction), oxidative stress (H2O2), high temperature (37°C), ethanol, and salt (NaCl). The frequency of LOH increased significantly in all environments including calorie restriction relative to the control (YPD). Interestingly, the percentage of the genome covered by LOH varied significantly depending on the condition. For example, the LOH tracts seen in calorie restriction conditions were significantly shorter than those observed in blue light exposure that rapidly homozygotized the genome. We also report a unique mutational signature of blue light exposure comprising LOH, small indels, large deletions and transversion mutations (G:C > T:A; G:C > C:G), with the latter likely to result from the photooxidation of guanine bases. Our results suggest ubiquitous environmental conditions cause LOH but result in distinct mutational signatures due to the type of damage induced and the pathways used to repair them.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011692"},"PeriodicalIF":4.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coordinated transcriptomic and metabolomic responses in rice reveal lignin-based physical barriers as key mechanisms of nonhost resistance to rust fungi.","authors":"Ce Zhang, Liru Jian, Tao Guan, Yiping Wang, Huihui Pang, Yiqian Xu, Yaoyao Xing, Jiawen Wang, Zhensheng Kang, Jing Zhao","doi":"10.1371/journal.pgen.1011679","DOIUrl":"10.1371/journal.pgen.1011679","url":null,"abstract":"<p><p>Nonhost resistance (NHR) serves as a fundamental defense response in plants against non-adapted pathogens, yet its underlying molecular mechanisms remain poorly understood. This study investigates the rice-Pst (Puccinia striiformis f. sp. tritici) interaction using integrated transcriptomic and metabolomic analyses to unravel the temporal dynamics of gene expression and metabolite changes associated with NHR. Our findings reveal a temporally coordinated activation of defense responses, with early induction of receptor-like kinases (RLKs) and hypersensitive response proteins, followed by later activation of jasmonic acid and systemic acquired resistance pathways, along with the accumulation of amino acids and other phenolic compounds. Notably, metabolic pathways related to cell wall reinforcement were significantly upregulated during Pst infection, highlighted by enhanced lignin biosynthesis (phenylpropanoid pathway), nucleotide sugar metabolism, and tryptophan pathways. Rice mutants deficient in genes involved in lignin biosynthesis (OsPAL3, Os4CL3, Os4CL5, and OsCCoAOMT) displayed reduced lignin deposition at infection sites and compromised resistance to Pst, underscoring a critical role of lignin-based physical barriers in NHR. This study provides novel insights into the molecular framework of rice NHR, emphasizing the pivotal role of structural defenses in plant immunity.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011679"},"PeriodicalIF":4.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of eicosanoid signaling in Drosophila development.","authors":"Daiki Fujinaga, Cebrina Nolan, Naoki Yamanaka","doi":"10.1371/journal.pgen.1011705","DOIUrl":"10.1371/journal.pgen.1011705","url":null,"abstract":"<p><p>20-carbon fatty acid-derived eicosanoids are versatile signaling oxylipins in mammals. In particular, a group of eicosanoids termed prostanoids are involved in multiple physiological processes, such as reproduction and immune responses. Although some eicosanoids such as prostaglandin E2 (PGE2) have been detected in some insect species, molecular mechanisms of eicosanoid synthesis and signal transduction in insects have not been thoroughly investigated. Our phylogenetic analysis indicated that, in clear contrast to the presence of numerous receptors for oxylipins and other lipid mediators in humans, the Drosophila genome only possesses a single ortholog of such receptors, which is homologous to human prostanoid receptors. This G protein-coupled receptor, named Prostaglandin Receptor or PGR, is activated by PGE2 and its isomer PGD2 in Drosophila S2 cells. PGR mutant flies die as pharate adults with insufficient tracheal development, which can be rescued by supplying high oxygen. Consistent with this, through a comprehensive mutagenesis approach, we identified a Drosophila PGE synthase whose mutants show similar pharate adult lethality with hypoxia responses. Drosophila thus has a highly simplified eicosanoid signaling pathway as compared to humans, and it may provide an ideal model system for investigating evolutionarily conserved aspects of eicosanoid signaling.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011705"},"PeriodicalIF":4.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroitin sulfate regulates proliferation of Drosophila intestinal stem cells.","authors":"Collin Knudsen, Ayano Moriya, Eriko Nakato, Rishi Gulati, Takuya Akiyama, Hiroshi Nakato","doi":"10.1371/journal.pgen.1011686","DOIUrl":"10.1371/journal.pgen.1011686","url":null,"abstract":"<p><p>The basement membrane (BM) plays critical roles in stem cell maintenance and activity control. Here we show that chondroitin sulfate (CS), a major component of the Drosophila midgut BM, is required for proper control of intestinal stem cells (ISCs). Loss of Chsy, a critical CS biosynthetic gene, resulted in elevated levels of ISC proliferation during homeostasis, leading to midgut hyperplasia. Regeneration assays demonstrated that Chsy mutant ISCs failed to properly downregulate mitotic activity at the end of regeneration. We also found that CS is essential for the barrier integrity to prevent leakage of the midgut epithelium. CS is known to be polymerized by the action of the complex of Chsy and another critical protein, Chondroitin polymerizing factor (Chpf). We found that Chpf mutants show increased ISC division during midgut homeostasis and regeneration, similar to Chsy mutants. As Chpf is induced by a tissue damage during regeneration, our data suggest that Chpf functions with Chsy to facilitate CS remodeling and stimulate tissue repair. We propose that the completion of the repair of CS-containing BM acts as a prerequisite to properly terminate the regeneration process.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011686"},"PeriodicalIF":4.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}